Method of preparing beta-thio-ethylamines



Patented Sept. 26, 1944 Mansion '1. Bogart, New York, and Edward J. Mills, Jr., New Rochelle, N. Y., asslgnors to E. R. Squibb 0; Sons, New york, N. Y., a corporation oi New York No Drawing. Application May 11, 1940,

' Serial No. 834,581

3 Claims. (cued-sea This invention relates to, and has tor its ob- Ject the provision of, a simple and emdlent method of preparing ,e-thio-ethylamines of the general formula especially p-mercapto-ethylamines oi the general formula a s CH-CHrNH1 wherein R and R represent each a member of Example 1 I A well-cooled 10% solution'of ethyleneimine (B. P. 54-56" C.) in 95% ethyl alcohol is added the group consisting of hydrogen, aliphatic (preierably lower alkyl) groups, aromatic (preierably phenyl) groups. and araliphatic (preferably phenyl-lower-alkyl) groups. Such compounds, especially the p-mercapto-ethylamines, are valuable intermediates for the production of medicinally and otherwise utilizable compounds. Thus, p-mercapto-ethylamine can be readily converted by oxidation into cystamine [bis-(,6- amino-ethyl) -disulfide], and both of these inexpenslvely-produced compounds can be used for the production-at a much lower cost than hitherto-oi the corresponding suli'o acids, sulioxides, suli'ones, ure'ides, barbituric, acids, pyrimidines, purines, and the like.

The process of this invention essentially comprises reacting a compound of the general foreneimine" being employed herein to embrace not only R-ethylen'eimine strictly so called (in which the R is attached to a carbon atom) but also the equally operative ,e-R-vinylainine. The heretofore-reported interaction of hydrogen sulfide and ethyleneimine-Gabriel and Eschenbach, Ber. 30, 2497, passed hydrogen sulfidethrough ethyleneimlne to produce bis-(,o-amino-ethyllsulfide-was under qualitatively diflerent conditions.

Iln the practice of this invention. hydrogen sulfide and ethyleneimine may be interacted in mula R'SH with an R-ethyleneimine in a solvent for the reactants-the term "R-ethylslowly to an equal volume of well-stirred 95% ethyl alcohol previously saturated with hydrogen sulfide and cooled to 0 C. During this addition, the temperature of the mixtureis held at 09 C., and a current of hydrogen sulfide is kept passing through continuously. After the addition of the ethyleneimine is completed, the hydrogen sulfide current is maintained for 10 or 15 minutes. Excess hydrogen sulfide is removed from the cold mixture by reducing the pressure.

amine begins to separate as a white crystalline solid. The mixture is then cooled to 0 C., the crystalline solid rapidly filtered out, washed once with petroleum ether, dried, and stored in an inert atmosphere, to prevent its oxidation to the disulflde. The white crystalline product thus obtained usually melts at about 97-98.5 C. (corn) and can be further purified if a M. P. of 99-l00 C. for the pure substance.

' Example 2 To alreaction mixture obtained as detailed in the foregoing example, there is added an equal volume of 95% ethanol saturated with HCl. The solution is then concentrated, in an inert atmosphere and under reduced pressure, to a viscous syrup, absolute ethanol is added and the solution cooled. The p-mereaptmethylamine hydrochloride which separates is removed, washed with a small quantity of chilled absolute ethanol, and dried. The product is a white crystalline solid melting at about 70.2-70.'l C. (corn) Gabriel and Leupold (Ber. 31, 2837) gave a melting point of -72 C. for this compound. The salt may-be converted into the free amine in the conventional manner.

The yield of p-mercapto-ethylamine obtained by the foregoing procedures is -95% of the thzgretical (calculated on the ethyleneimine us Maniiestly, other p-mercapto-ethylamines oi the general formula given hereinbefore may be prepared by the procedures of the foregoing examples, using the corresponding R -ethyleneimine inplace of ethyleneimine. Thus, by using propenylamine, p-methyl ,8 mercapto ethylamine can be prepared; by using styrylamine,

v,er phenyl-p-mercapto-ethylamine can be pre- The reaction mixture is concentrated to' a small volume in an inert atmosphere under re- 1 duced pressure, until the p-mercapto-ethylry, Gabriel and Colman (Ben, 45, 1644), reported bodied, within the scope of the -appended claims.

We claim: 1. The method of preparing a p-mercaptoethylamine of the general formula HB-OH-CHr-NH:

aassnae v V which comprises slowlyadding an R-ethyleneimine to a solution of hydrogen sulfide in a I01- vent tor the R-ethyleneimine, wherein R represents a member or the group consisting or hydrogen, lower alkyl. and phenyl.

2. The method of preparing a p-mercaptoethylamine of the general formula which comprises slowly adding a solution of an R-ethyleneimine, wherein R represents a memher or the group consisting of hydrogen, lower alkyl, and phenyl, to a solution of hydrogen sulflde.

3. The method of preparing p-mercapto-ethylamine which comprises slowly adding a solution of ethyleneimine to a solution of hydrogen suliide.

MARBTON T. IBOGERT.

J. MILLS, Ja. 

